Modulation of COX-2 and NADPH oxidase-4 by alpha-lipoic acid ameliorates busulfan-induced pulmonary injury in rats

Mona G Elhadidy; Ahlam Elmasry; Hassan Reda Hassan Elsayed; Mohammad El-Nablaway; Shereen Hamed; Mahmoud M Elalfy; Mohammed R Rabei

doi:10.1016/j.heliyon.2021.e08171

Modulation of COX-2 and NADPH oxidase-4 by alpha-lipoic acid ameliorates busulfan-induced pulmonary injury in rats

Heliyon. 2021 Oct 13;7(10):e08171. doi: 10.1016/j.heliyon.2021.e08171. eCollection 2021 Oct.

Authors

Mona G Elhadidy^{1

2}, Ahlam Elmasry³, Hassan Reda Hassan Elsayed⁴, Mohammad El-Nablaway⁵, Shereen Hamed⁶, Mahmoud M Elalfy⁷, Mohammed R Rabei⁸

Affiliations

¹ Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt.
² Department of Medical Physiology, College of Medicine, Al-Baha University, Saudi Arabia.
³ Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Egypt.
⁴ Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Egypt.
⁵ Medical Biochemistry Department, Faculty of Medicine, Mansoura University, Egypt.
⁶ Department of Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Egypt.
⁷ Department of Forensic and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Egypt.
⁸ Department of Medical physiology, Faculty of Medicine, King Salman International University, South Sinai, Egypt.

Abstract

Aims: This study aimed to explore the potential protective effect of α-lipoic acid on busulfan-induced pulmonary fibrosis in rats.

Main methods: Eighteen adult male rats were divided into 3 groups; control, busulfan, and busulfan plus α-lipoic acid groups. Lung index ratio, serum level of proinflammatory cytokine were assessed. The activities of antioxidant enzymes and lipid peroxidation products were estimated in the lung tissues in addition to the histopathological analyses. The deposition of the collagen in the lung tissues was evaluated by Sirius red staining. The expressions of α-smooth muscle actin (α-SMA), TNF-α, and Caspase 3 were determined immunohistochemically. The pulmonary expression of COX-2 and NOX-4 mRNA was assessed using qRT-PCR.

Key findings: Administration of ALA significantly protect the lung against BUS-induced pulmonary fibrosis, besides the upregulation of antioxidants, and downregulation of pro-inflammatory cytokines. Also, it reduced collagen deposition that associated with a decreased expression of α-SMA, TNF-α, and Caspase 3 in the lung tissues. Moreover, ALA significantly upregulated the expression of COX-2 concomitant with the downregulation of elevated NOX-4.

Significance: ALA attenuates the lung cytotoxicity of busulfan through its anti-inflammatory, anti-apoptotic, and antifibrotic effects that may be mediated by upregulation of COX-2 and downregulation of NOX-4.

Keywords: Apoptosis; Busulfan; COX-2; NOX-4; Pulmonary fibrosis; α-lipoic acid (ALA).